A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action.
14-3-3
ERα
protein-protein interaction
stabilizers
supramolecular systems
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
23 03 2020
23 03 2020
Historique:
received:
13
11
2019
pubmed:
10
12
2019
medline:
18
3
2021
entrez:
10
12
2019
Statut:
ppublish
Résumé
We report on a stabilizer of the interaction between 14-3-3ζ and the Estrogen Receptor alpha (ERα). ERα is a driver in the majority of breast cancers and 14-3-3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein-protein interaction (PPI) an interesting strategy. The stabilizer (1) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14-3-3ζ/ERα interaction synergistically with the natural product Fusicoccin-A and was thus hypothesized to bind to a different site. This is supported by computational analysis of 1 binding to the binary complex of 14-3-3 and an ERα-derived phosphopeptide. Furthermore, 1 shows selectivity towards 14-3-3ζ/ERα interaction over other 14-3-3 client-derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14-3-3ζ/ERα PPI stabilizer.
Identifiants
pubmed: 31814236
doi: 10.1002/anie.201914517
pmc: PMC7155037
doi:
Substances chimiques
14-3-3 Proteins
0
Estrogen Receptor alpha
0
Glycosides
0
Peptides
0
fusicoccin
20108-30-9
Arginine
94ZLA3W45F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5284-5287Informations de copyright
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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